Substituted epoxyeicosatrienoic acid (EET) analogs for treatment of kidney disease

Abstract

Described here are EET analogs conjugated to folate receptor ligands such as folic acid or folic acid analogs recognized by and selectively bound by folate receptors and other folate binding proteins and the use of such conjugated EET analogs for targeted delivery of therapeutic agents to folate-receptor bearing cell populations. More particularly, provided herein are EET analogs conjugated to folate receptor ligands and uses of such conjugated EET analogs as kidney targeted therapeutics.

We claim: 
     
       1. A compound having the formula: 
       
         
           
           
               
               
           
         
       
     
     
       2. A pharmaceutical composition comprising the compound of  claim 1  and at least one pharmaceutically acceptable carrier, excipient, or diluent. 
     
     
       3. A method for modulating folate receptor binding in a cell, wherein the method comprises contacting the cell with a therapeutically effective amount of the pharmaceutical composition of  claim 2 . 
     
     
       4. A method for reducing nephrotoxicity in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of the pharmaceutical composition of  claim 2 . 
     
     
       5. The method of  claim 4 , wherein the nephrotoxicity is cisplatin-induced. 
     
     
       6. The method of  claim 4 , wherein the nephrotoxicity is drug-induced. 
     
     
       7. A method for treating kidney disease in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of the pharmaceutical composition of  claim 2 . 
     
     
       8. A compound having the formula: 
       
         
           
           
               
               
           
         
       
     
     
       9. A pharmaceutical composition comprising the compound of  claim 8  and at least one pharmaceutically acceptable carrier, excipient, or diluent.